Five years age we found that 5'-nucleotidase (5'N) activity was not detectable or markedly diminished in the lymphocytes from most patients with chronic lymphocytic leukemia (CLL). Recent studies have shown the lack of immunoreactive protein in these cells. This decrease is irreversible and unrelated to B/T subpopulations. Recently, we found a reversible decline in adenosine deaminase activity in CLL. Future studies will extend these observations along the following lines: 1) The regulation of 5'N will be investigated in tissue culture systems. 2) Family studies designed to determine the genetic control of lymphocyte 5'N activity are planned. 3) Further clinical studies are under way to determine whether the loss of 5'N activity is an epiphenomenon of the leukemic state or a pre-leukemic biochemical characteristic. These studies will clarify the significance of the 5'N alterations in CLL and explore the implications of adenosine deaminase deficiency on purine metabolism in this disorder. 4) The inhibitory effects and metabolism of adenosine on normal and CLL lymphocytes will be compared. 5) The relationship of the adenosine inhibitory effects to the adenyl cyclase and cyclic nucleotide-protein kinase interactions are under study in normal and CLL lymphocytes.